Child abuse rips genes

Again on the pet peeve of flu shots for healthy people and antibacterial soaps - a recent report shows that 98% of influenza A strains in the US, and 100% in Canada, are resistant to the flu drug Tamiflu. Hardly surprising given that we've treated about 50 million people with it, and chances are that most of them were improperly medicated.

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So once again, my boss is making waves in the news, this time with actual science, which is a bit of relief. A study mostly carried out by one of our post-doctoral fellows has been getting a great amount of media attention, as it's a very interesting finding. He shows that suicide victims with a history of abuse carry a higher amount of an alteration to DNA structure (but not sequence) that controls the expression of a gene involved in the stress response (glucocorticoid receptor Nr3c1 promoter methylation in hippocampus, for those keeping track). This alteration may "silence" the gene and have rendered these people more subject to anxiety and other negative effects of stress.

My favorite thing about this study has been the press, particularly the BBC's headline of "Child abuse 'impacts stress gene'." One thing I can't figure out about the BBC is why they put those little single quotation marks around a couple words in about 50% of their headlines: "Staff 'too timid' on child abuse," "'Ethical' stem cell hope," or "Veterans at 'higher suicide risk.'"

What do these little quotes mean? They certainly aren't a direct quotes, as my boss would beat you about the head and shoulders for saying the glucocorticoid receptor is a stress gene. They seem to serve no purpose other than to confuse people who want to use real quotation marks on their headlines for citation purposes.

In any case, people tend to take findings like this WAY too far to support whatever point of view that they have. Take the CBC's angle on the story, for example. We've got a journalist claiming that "in a way... the men were programmed to be more vulnerable to overwhelming feelings of despair," which didn't come from any of the researchers on this study (trust me, I know them all personally). Then we have a pharmacologist saying we should aim to "identify these people and then probably offer them some sort of intervention," which is interesting because 1) we have no indication whatsoever that the methylation changes actually cause the suicides, and 2) it's a real bastard trying to get those samples out of living human brains.

From the blogosphere, I think my favorite quote so far has been something along the lines of how obvious it is that abuse is bad and should we really spend millions on research to prove it? I can hardly claim impartiality here, seeing as how my salary gets paid directly from those grants, but the answer is "yes we should, because it's not obvious at all."

OK, so it's obvious that beating your kids is bad (unless you're Russell Peters), but what isn't obvious is why, on a biological level, child abuse is harmful for development. Is it obvious that DNA methylation patterns along the Nr3c1 promoter would be different in the hippocampus of abused suicide victims? Is it obvious that beating your children is like picking up their DNA and twisting it around? Is it obvious why legislators feel like there has to be some kind of biological correlate in order to make a disease somehow legitimate?

We're on your side, people. Don't accuse us of wasting government funds by proving the "obvious." If it's so obvious, then I'm in the comments section waiting patiently for a scientific explanation of the precise gene-environment interactions leading up to suicide.

Remixing memories

I'm thinking that The Globe and Mail has been checking out my blog, seeing this article from earlier in the week talking about the things from my last post. Particularly how other countries are pumping money into research while Canada is cutting. Interestingly, they interviewed my PhD supervisor, who is apparently "one of Canada's top scientists".

I'm pleased how closely his opinions follow mine, and that they're publishing them in the Globe and Mail. I'm a bit disturbed about being so similar to my boss, though. I'm also disturbed that he apparently has fantasies of moving to Signapore...

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A genetic therapy approach to treating AIDS that I blogged about last summer is currently recruiting for its first clinical trial. This is pretty incredibly quick, but it seems very safe - take some of a patient's blood, take out the T-cells, culture them, insert the gene, grow a whole pile of the modified cells, and then return them to the patient. This follows on the footsteps of another successful trial of gene therapy for AIDS treatments.

The risks of these treatments seem minimal. The gene transfer isn't contagious to other cells, and the T-cells come from the patient's own body so there should be no risk of rejection. Assuming the cells aren't grown in an animal serum, which could induce a rejection response in patients. But I imagine these guys know what they're doing.

Of course, the guys injecting a Russian boy with stem cells also knew what they were doing, and they knew the risks. Turns out they lost this bet - the kid developed extensive tumours throughout his nervous system. While this was a predicted potential side effect, I don't think anyone was expecting this to go so spectacularly wrong.

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If there's one thing I've been wanting to blog about this week, it's this story about using a heart medication (propranalol, a beta-blocker) to "block bad memories." People are going buck-wild about this - I even saw it on Facebook (I have some geeky friends). But the study is not all it's cracked up to be.

The researchers conditioned people to be "afraid" of spiders by showing them pictures of spiders and then shocking them, a Pavlovian paradigm that couples a neutral stimulus (spider) to an averse stimulus (shock), and transfers the unpleasant feeling associated with the shock to the spider. The drug was able to reverse this conditioning, so people no longer had an adverse response to the spiders. And now it's being touted as a treatment for PTSD and anxiety disorders.

First of all, I would like someone to explain to me and a couple of war veterans exactly how shocking someone while looking at pictures of spiders is anything remotely like traumatic experiences like losing a limb in a firefight or having your friend's brains blown out all over you. Or even like being in a car crash.

Secondly, even something like a phobia against an object (say, spiders) isn't like a conditioned association. In fact, it's the opposite. The reason it's a phobia is precisely because it's an unconditioned and irrational fear of an object. Show me a trial with arachnophobics on propanalol viewing pictures of tarantulas and I don't think we'll see such stunning claims being made.

The idea is that when we remember things, we take the representation out of long-term storage in our brains and move it into "working memory," a sort of RAM buffer memory for your brain. When we're done with it, it gets re-programmed back into the long-term storage. If we can remove the bad associations from the memory before we code it back into long-term storage, then we can remove some of the anxiety and pathology that comes from remembering it.

I, for one, am not sure that this will work. I think that removing a simple conditioned association is a lot different from removing the particularly vivid memories that many PTSD patients have, and that the emotional component of these memories is much more intense than a simple shock to the finger. I think the biochemical underpinnings are significantly more complicated than simple noradrenaline release as well. That being said, we can condition men to respond sexually to an old boot, but again I would argue that this neither a complex behaviour nor particularly difficult to accomplish. Now if we could do it in women, then we'd be on to something.

I'm not sure what it will take to "erase" these memories, but I refer you back to an earlier post I made on memory manipulation and Joe Tsien's quote: "All memories, including the painful emotional memories, have their purposes. We learn great lessons from those memories or experiences so we can avoid making the same kinds of mistakes again, and help us to adapt down the road."

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My other blog, for those who are interested, is up. The first post is enititled "Douglas Zombies Need Brains." And if that doesn't pique your interest, then I don't want you reading it anyways.